Process for preparing sulfonamides



' a period of 80 minutes, by maintaining the t'm Patented May 18, 1948 Y OFFICE 23411671 finesse fioit' hint-Annie statements loiiliinfg Bronx, N; i, assignor to Sun Ch'emical"Corporation, a corporation of nemesis it? Drarving 1 pplication March 11, 1944 Serial No. 526,132 5 oiaims. (o1. z'sb' sst) This invention relates, to, processes for t e "aring sulfonamide derivatives" of amin'oaryl compounds;

It is an object of the pie ent inven'ti W vide processes for wo an? aminoary s ton 5 mi i V Another bject of the present inv provide processes for preparifi ar'n fonamides from aminoaryl hydro chlorsulfonation and subsequent Another object of th'j present in 'ent v de ro s f repai'i l l a nioarn w' om amides characterized by simplicity and economy of operation and of chemical reacti'o Other objects of the invention will from the specificatio'rrand appendedcl p I now havefound that aminoarylsulfon I es,- compoun'ds of great utility and v me in ma y i dustrial applicationscan be pro red by relating. 1y simple and economical methodsfmethods which now make readily availablesuchhihly valuable and useful materials of great im ortance, In the practicing' ofmy nvention I have discovered that y proper react ons; ot chl'orsul fonation and animation, aminoa'ryl hydroelerides can be converted directlyinto sfu'lic'na derivatives-thus pro'vidi' g such 51 m useful materials available for abpli c'ation as s nor for further conversion into other usefulproducts;

A illustrative em di 9f UPbSSfiI 1 erations, some examples hereinafter given representative of practical; useful, commercial operations. Example 1.-In a cc. of chlorsulfonic acid and th thereto 410 grams of 2-arni'no ride under conditions such that predominantly a" monosulfonyl chloride compound is formed 'gari'd with the above described ma ena1 ,s cp's rt1- results are secured by addin' r the hydrochloride over 41) ran va e e ig ne added perature in the rea" tio athfbeldwflQ-{Cga by cooling, and by mainta mg the reactiohniixtiire under .interreact'iv'e agitation, asst stirring, throughout the addition period. When all of t e hydrochloride is ncorporated, the teiiijiimtiir a the reaction mixture is raised to iii)" C; as t3 heating, and the mixture maintained tinder iiiterreactive agitation at that temperature (were period of three hours to insure completion of the monosulfonation reaction. The efitir mixture is then cooled to roomte npe atur tenements the preparation of 2'-amiriobiphnyl i'-su1fony1 ch16- ride. I

The sulfonyl chloride reaction product thus ob 2 tained" is then added to 3200 cc. of concentrated" ammonia (26. B.) inla reaction vessel, under re action conditions such that predominantly aniig nationof the sulfoni'd'e chloride occurs,-and,wit'h the quantities of materials described, successful reaction conditions include maintaining the ammonia-sulfonyi chloride mixture under reaction agitation conditions; asby stirring, and maintaining the reaction temperature between 0 C. and

? 8 C'., as by refrigeration, and by maintainingsuch agitation for a period of four hours after addition o'f the sulfonyl chloride is completed. The,

precipitatewhich forms is separated from the liquid constituents, as by filtration, and the separated solid material washed with several portions of water until the washings show n'otrace of chloride or sulfate ion, examination of the washing for these ions being conducted by the well known chemical tests. The Washed solid material is then dried, convenient1y at 0., to furnish 2'- aminobiphenyl-l'-sulfonamide in a substantially pure state. U

Example 2.- T.o a reaction vessel containing 80 cc, of chlorsulfonic acid is added 50 grams of 4- ami'n'obiphenyl hydrochloride, under conditions such that predominantly a monosulfonyl chloride is ormedand with the quantities described, successful results are obtained by maintaining the reaction mixture under interreactive agita= tion, as by stirring, throughout the addition period, by maintaining the temperature of the reaction mixture below 10 0., as by refrigeration, and by adding the hydrochloride over a period of 40 minutes. When all of the hydrochloride has been incorporated, the mixture is then heated at C. over a period of three hours, to complete themonosulfonation reaction, and subsequently cooled to approximately room temperature (about 20 C.) r

The reaction mixture thus obtained is added to a reaction vessel containing 530 cc. of concern tra'ted ammonia (26f B.) under conditions such that am ination of the sulfonyl chloride occursand with the quantities above described, successful results are obtained by maintaining the reaction mixture between 0 C. and 8 C. throughout the addition period, and by maintaining the admixture under reaction agitation conditions'as by stirring; when all of the sulfonyl chloride has been incorporated, the mixture is maintained under such agitation for'an additional period of several hours, to complete the formation of a sulfonar'nide precipitate. This precipitate is then separated from the reaction admixture, as by filtration, and the solid material thus obtained washed with several portions of hot water until the washings show no trace of chloride or sulfate ion. The washed solid is then dried, convenient- 1y at 95 C., to remove water remaining. In this way there is obtained 4-aminobiphenyl-4'-sulion-amide.

The process or the present invention, exam ples of which are hereinbefore given, is applicable also to the preparation of arylsulfonamides, in which the starting material is an aryl compound containing a single ring structure, and as illustrative of successful operation, using the monoaryl compounds, the following example is wen:

g Example 3.-o-Toluidine hydrochloride (14.4 grams) is incorporated in a reaction vessel containing 32 cc. of chlorsulfonic acid, under conditions such that a monosulfonyl chloride is formed-and with the quantities above described, successful results are secured by maintaining the admixture under interreactive agitation, as by stirring, throu hout the addition period, by maintaining the reaction mixture below 7 0., as by refrigeration, and .by incorporating the hydrochloride over a period of twenty-five minutes. To complete the .monosulfonation reactio the admixture is then heated under reaction agitation conditions for two hours at 90 C. and subsequently cooled to room temperature.

The resulting admixture containin sulfonyl chloride is then added to a reaction vessel containing 300 cc. of concentrated ammonia (26 Be.) under conditions such that amination cf the sulfonyl chloride is efiected-and with the materials described, such amination occurs when the reaction mixture is maintained under agitation, as by stirring, throughout the addition p. riod, and the temperature of the reaction materials maintained between C. and 11 0., as.

by refrigeration. The mixture secured is maintained under agitation for an additional period of several hours to complete the formation of a sulfon-amide precipitate. The precipitate is then separated from the remainder of materials present, as by filtration, and subsequently washed with several portions .of water to remove chloride and sulfate ion. The solid product is then dried at .80" C. to remove the water remaining. The dried product obtained is ot oluidine-psulfon a mide.

The illustrative examples hereinbefore given, as representative of successful practicing .of the present invention, furnish .a convenient and relatively simple method for preparing aminoarylsulfonamides. By employing the processes herein described, it becomes possible to prepare such valuable products without the necessity of utilizing cumbersome and expensive and highly complicated procedures heretofore necessary to prepare the highly valuable sulfonamide compounds. For example, it is now unnecessary to use procedures which involve the use of acetic anhydride in the preparation of such compounds, a, material which is relatively expensive and which, furthermore, cannot .be recovered .as such from the reaction product, .but which is destroyed in the reaction processes, though it does not appear as a chemical constituent part of the final product, nor is it necessary to employ reaction processes which involve utilization of materials such as phosphorus pentachloride, an expensive material which is vdifiicult to handle and which involves utilization of expensive and relatively inefiicientrprocedures.

While the processes for preparing the products herein described constitute preferred embodiments of the invention, it will be understood that changes may be made therein without departing from the scope of the invention, as defined in the appended claims.

What is claimed is:

1. The process for preparing an aminobiaryl sulfonamide which consists in the steps of chlorsulfonation of an aminoblaryl hydrochloride with chlorsulfonic acid in the ratio of approximately 1 mol of said aminobiaryl hydrochloride to approximately 5 mols of said chlorsulfonic acid and at a temperature below 7 C. to eifect formation of a monosultonyl chloride material in reaction admixture, thereafter aminating said monosulfonyl chloride material with ammonia, whereby a sulfonamide is formed, and thereafter separating and recovering said sulfonamide.

2. The process for preparing an aminoaryl monosulfonamide, which consists in the steps of forming a reaction admixture containing an aminoaryl monosulfonyl chloride by effecting reaction of chlorsulfonic acid with an aminoaryl hydrochloride by addition of said aminoaryl hydrochloride to said chlorsulfonic acid in the ratio of approximately 1 mol of said aminoaryl hydrochloride to approximately 5 mols .of said chlorsulfonic acid and at a temperature below 7 CL, whereby said aminoaryl monosulfonyl chloride is formed in reaction admixture, thereafter aminating said reaction admixture with ammonia, whereby an aminoaryl monosulton-amide is formed in reaction admixture, and thereafter separating and recovering said aminoaryl monosulfonamide.

3. The process for preparing 2-aminobiphenyl- 4-su1fonamide, which consists in the steps of forming .a reaction admixture containing 2 aminobiphenylt -sulfonyl chloride by eflecting reaction of chlorsulfonic acid with 2-ami-nobiphenyl hydrochloride by addition of said 2- aminobiphenyl hydrochloride to chlorsulfonic acid in the ratio .of approximately 1 mol of '2- aminobiphenyl hydrochloride to approximately 5 mols of chlorsulfonic acid and at a temperature below 10 C., whereby said Z-aminobiphenyh sulfonyl chlorideis formed in reaction admixture, thereafter aminating said reaction admixture with ammonia, whereby 2-aminobiphenyl-4- sulfonamide is formed in reaction admixture, and thereafter separating and recovering said 2-aminobiphenyl-4i-sulfonamide 4. The process for preparing 4-aminobi-phenyl- 4'-sulfonamide, which consists in the steps of forming a reaction admixture containing 4- aminobiphenyl-4'-sulfony1 chloride by effecting reaction of chlorsulfon-ic acid with asaminobiphenyl hydrochloride by addition of said 4- .aminobiphenyl hydrochloride to chlorsulfonic acid in the ratio of 1 mol of a-biphenyl hydrochloride acid to approximately 5 mols of chlorsulfonic acid and at a temperature below 10 C whereby said l-aminobiphenylt'-sulfony1 chloride is formed in reaction admixture, thereafter aminating said reaction admixture with ammonia, whereby 4-aminobiphenyl-4'-sultonamide is formed in reaction admixture, and thereafter separating and recovering said 4-aminobiphenyl-4 -sulfonamide.

5. The process for preparing o-toluidine p sulfonam-ide, which consists in the steps of forming a reaction admixture containing o-to'luidine-psulfonyl chloride by effecting reaction of ,chlore sulfonic acid with o-toluidine hydrochloride by addition of Said .O-toluidine hydrochloride to said chlorsulfonic acid in the ratio of approximately 1 mol of o-toluidine hydrochloride to approxi- FOREIGN PATENTS mately 5 mols of chlorsuifonic acid and at a tem- Number Country Date perature below 7 0., whereby o-toluidine-p-sul- 167,377 Switzerland May 1, 1934 fonyl chloride is formed in reaction admixture, 5 OTHER REFERENCES thereafter aminati-ng said reaction admixture t ammonia, whereby o tol idine lfo Cumming et al., Systematic Organic Chemistry,

mide is formed in reaction admixture, and there- 1926, Page after separating and recovering said o-toluidine- Chemical Abstl' 22, (1923), Pages 231 p-sulfonamide. and 1972- ALEXANDER H POPKHL Sldgewlcks Organic Chemistry Of Nitrogen (1937), page 157. REFERENCES CITED Chemical Abstracts, vol. 35 (1941), pages 5458- Th r 11 1 r r a i m 5459' 4 8 W m re erences are e Beilstein, Handbuch der Org. Chemie, vol. XIV, file of this patent: s page 686. I

UNII'ED STATES PATENTS Organic Syntheses, Collective, Volume I Numbel; Name Date (1932), pages 8 and 9.

1,911,719 Schweitzer May 30, 1933 

